Differences In Luteinizing Hormone Research Articles

Sex differences in luteinizing hormone aggravates Aβ deposition in APP/PS1 and Aβ1-42-induced mouse models of Alzheimer's disease

Alzheimer's disease (AD) exhibits a higher incidence rate among older women, and dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis during aging is associated with cognitive impairments and the development of dementia. luteinizing hormone (LH) has an important role in CNS function, such as mediating neuronal pregnenolone production, and modulating neuronal plasticity and cognition. The sex differences in LH and its impact on Aβ deposition in AD individuals remain unclear, with no reported specific mechanisms. Here, we show through data mining that LH-related pathways are significantly enriched in female AD patients. Additionally, LH levels are elevated in female AD patients and exhibit a negative correlation with cognitive levels but a positive correlation with AD pathology levels, and females exhibit a greater extent of AD pathology, such as Aβ deposition. In vivo, we observed that the exogenous injection of LH exacerbated behavioral impairments induced by Aβ1-42 in mice. LH injection resulted in worsened neuronal damage and increased Aβ deposition. In SH-SY5Y cells, co-administration of LH with Aβ further exacerbated Aβ-induced neuronal damage. Furthermore, LH can dose-dependently decrease the levels of NEP and LHR proteins while increasing the expression of GFAP and IBA1 in vivo and in vitro. Taken together, these results indicate that LH can exacerbate cognitive impairment and neuronal damage in mice by increasing Aβ deposition. The potential mechanism may involve the reduction of NEP and LHR expression, along with the exacerbation of Aβ-induced inflammation.

Differential diagnosis of precocious puberty in girls during the COVID-19 pandemic: a pilot study

BackgroundTo investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19 pandemic. We explored predicted adult height (PAH) discrepancy to guide appropriate diagnosis and treatment.MethodsFrom January 2020 to December 2021, Chinese girls aged 6 to 8 years with precocious puberty were recruited. They were divided into IPT and CPP groups. Clinical characteristics, including height, weight, body mass index (BMI), basal luteinizing hormone (LH), oestradiol, uterine length and volume, follicle numbers (d > 4 mm) and bone age (BA) were recorded. We analysed differential diagnosis and PAH discrepancy in both groups. Binary logistic regression analysis was used to explore risk factors for CPP, and receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of related indexes.ResultsSixty patients, including 40 girls with IPT and 20 girls with CPP, were recruited. The prevalence of overweight and obesity in the entire cohort was 25% (15/60) and was significantly higher in IPT than CPP, 32.5% (13/40) vs. 10% (2/20), respectively (P=0.045). There were significant differences in LH, uterine volume, follicle numbers and BA (P<0.05). The impaired PAH of IPT and CPP was 0.01 ± 1.19 SD and 0.62 ± 0.94 SD with significant differences (P=0.047). Logistic regression analysis showed that LH and follicle numbers were independent risk factors for CPP. The ROC curve showed that the area under the curve (AUC) of LH and follicle numbers were 0.823 and 0.697. The sensitivity and specificity of LH with a cut off of 0.285 IU/L were 78.9% and 77.8%. The sensitivity and specificity of follicle numbers with a cut off of 3.5 were 89.5% and 52.8%.ConclusionThe prevalence of overweight and obesity in 6- to 8-year-old girls with precocious puberty was high. Auxological data should not be used in the differential diagnosis of IPT and CPP. Basal LH above 0.285 IU/L and follicle numbers greater than 4 were important features suggestive of CPP. PAH was impaired in individuals with CPP, but it was not impaired in individuals with IPT.

Theeffect of concentrated pomegranate juice on biomarkers ofinflammation, oxidative stress, and sex hormones in overweight and obese women with polycystic ovary syndrome: Arandomized controlled trial.

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder. Pomegranate juice (PJ) has been known to play anti-inflammatory and antioxidant roles. However, the effects of PJ on inflammation, oxidative stress, and sex hormones in PCOS patients are very little studied, and thus more studies are needed. This randomized controlled trial enrolled 44 women diagnosed with PCOS according to the Rotterdam criteria, body mass index (BMI) ≥ 25 kg/m2 , and aged 18-40 years old. Participants were randomly assigned to take 45 ml/day of concentrated PJ or a control group without intervention. Some biomarkers of sex hormones, inflammation, and oxidative stress were quantified at baseline and after the 8-week intervention. Compared with the controls, serum testosterone levels were significantly decreased in overweight and obese women with PCOS who supplemented with concentrated PJ (-0.004 ± 0.013 vs. 0.039 ± 0.013, p= .039). However, we did not observe significant differences in luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) levels and inflammation and oxidative stress factors between the two groups after adjustment for confounding variables. An 8-week supplementation with concentrated PJ could effectively improve testosterone levels in overweight and obese women with PCOS. This study was registered at www.irct.ir (IRCT20191109045383N1).

Evaluation of factors predicting pregnancy by comparing successful IVF cycles with previous failed ones of the same patients in the same year

Aim: In this study, we aimed to examine the factors predicting pregnancy by comparing successful in vitro fertilization/ intracytoplasmic sperm injection (IVF)/(ICSI) fresh cycles with previous failed ones of the same patients in the same year. Materials and Methods: The study consisted of two groups, failed (n:283) and successful IVF fresh cycles (n:283) that applied one after another within the same year, thusly each woman acted under her own control. IVF treatment indications, antral follicle count, ovulation induction protocol type, initial and total gonadotropin dose, progesterone, and estradiol (E2) levels on the trigger day, the number of oocytes retrieved and mature oocytes, number of Grade 1, Grade 2, Grade 3 embryo, day of embryo transfer (ET), endometrial thickness on trigger and oocyte pick-up (OPU) day, embryo-fundus distance and beta-human chorionic gonadotropin (B-hCG) levels on the 10th day after the ET were measured. The same luteal phase support was administered in both groups. Results: Totally 566 cycles and 283 women were included in the study. There was a significant difference in luteinizing hormone (LH) levels on OPU day and number of grade 1 ET between the two groups, LH levels on OPU day and number of grade 1 ET were higher in successful IVF fresh cycles group (p&lt;0.05). Conclusion: Low serum LH levels on OPU day was associated with decreased pregnancy results. Increased IVF success was observed in grade 1 ET cycles.

Effects of letrozole co-treatment on the cumulative live-birth rate among normal responders in gonadotropin-releasing hormone antagonist cycles.

Studies have shown that letrozole cotreatment can improve clinical outcomes in high and poor responders in GnRH-antagonist protocol. However, whether letrozole is also beneficial to normal responders is not known. To investigate the clinical value of letrozole cotreatment during ovarian stimulation in vitro fertilization for normal ovarian reserve patients who were treated with the GnRH antagonist protocol, we conducted a retrospective study that based data from 1 January to 31 December 2017 for all IVF-ICSI GnRH-antagonist protocols. A total of 252 women who aged <40 years, FSH <10 IU/L on day 3 and antral follicle counting (AFC) >6 were included in the analysis (96 in the letrozole group and 156 in the no-letrozole group). The cumulative live-birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (cycles using fresh embryos and frozen-thawed embryos) among both groups. The initial gonadotropin (Gn) dosage and total Gn dosage were significantly lower and the number of days of Gn treatment was significantly fewer in the letrozole group than the non-letrozole group (p < 0.05). There were also significant between-group differences in luteinizing hormone, estradiol, and progesterone concentrations; and the number of metaphase II oocytes on the day of human chorionic gonadotropin treatment (p < 0.05). There was a significant difference in the implantation rate between the two groups that the letrozole group higher than the non-letrozole group (39.79 vs. 27.96%, p = 0.006), but there was no significant difference in the cumulative live-birth rate. The combination of letrozole with a GnRH antagonist may have no effect on the clinical pregnancy rate or cumulative live-birth rate in patients with a normal ovarian reserve. However, letrozole may increase the rate of embryo implantation and may reduce the requirement for exogenous gonadotrophins and, consequently, the cost of an IVF treatment cycle. In addition, the decreased estradiol level in the ovarian simulation by letrozole supports letrozole can be a safe solution for fertility preservation in estrogen-related cancer patients.

Progesterone and progesterone-induced blocking factor (PIBF) levels in non-obese women with polycystic ovary syndrome

Purpose: This study aimed to evaluate the level of progesterone and progesterone-induced blocking factor (PIBF), an immune mediator, in non-obese patients with polycystic ovary syndrome (PCOS).&#x0D; Materials and Methods: Totally 72 patients were recruited into study and divided into 2 groups: The first group was patients diagnosed with PCOS (n = 36) and the second was the healthy control group (n=36). The diagnosis of PCOS was made according to Rotterdam diagnostic criteria. All patients were 18–35 years old and non-obese (body mass index (BMI) &lt; 25 kg/m2). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), thyroid-stimulating hormone (TSH), prolactin (PRL), total testosterone, and dehydroepiandrostenedione sulfate (DHEA-S) levels were measured on the third day of the menstrual cycle. On the 21st day of the same menstrual period, fasting blood glucose, insulin, progesterone, and PIBF levels were measured. &#x0D; Results: Demographic and clinical characteristics of study participants were similar between the two groups. Serum FSH, E2, TSH, PRL, DHEA-S, total testosterone, fasting blood glucose, fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and hemoglobin A1c values were similar between the groups. Differences in LH, LH/FSH ratio, serum progesterone, and serum PIBF were statistically significant.&#x0D; Conclusion: Progesterone and PIBF levels decreased in non-obese PCOS patients. We suggest that even in the absence of obesity, which is the origin and enhancer of inflammation in PCOS, low PIBF as the underlying immunomodulator will drive complications.

Testicular torsion: its effect on autoimmunisation, pituitary\u2013testis axis and correlation with primary gonadal dysfunction in boys

BackgroundTorsion of the testis is an urgent surgical condition that endangers the viability of the gonad and the fertility of the patient. Our aim was to assess potential autoimmune processes and hormonal abnormalities in boys operated on due to that illness.MethodsThe authors evaluated the levels of antibodies against sperm and Leydig cells, concentrations of follicle-stimulating, luteinizing and anti-Müllerian hormone, testosterone, oestradiol and vascular endothelial growth factor in the serum in 28 boys operated on due to torsion of the testis. Patients’ sexual maturity was assessed according the Tanner scale (group G1, G4 and G5).ResultsNo antibodies against sperm or Leydig cells were found in the serum. Statistically significant differences in follicle-stimulating and anti-Müllerian hormone concentrations were observed in the G1, and they were higher in the study than in the control group. There were no statistically significant differences in luteinizing hormone, testosterone, oestradiol and vascular endothelial growth factor concentrations in the study group or control group. Testosterone concentration was unrelated to total testicular volume.ConclusionsResults did not confirm the autoimmune process in boys with torsion of the testis. The pituitary–testis axis seems to have sufficient compensation capabilities. However, study results suggest that primary gonadal dysfunction may predispose to torsion.ImpactSignificant differences exist between the literature data and own results on the formation of antibodies and hormonal changes due to testicular torsion in boys.It is a novel, prospective study on antibodies against sperms and Leydig cells in the serum and on hormonal processes occurring as a result of the testicular torsion from the prenatal period to the adolescence with division into pubertal groups.The study has revealed sufficient compensation capabilities of the pituitary–testis axis and no autoimmune process in boys with torsion of the testis.

Erectile Dysfunction, Testosterone Levels and Disease Activity in Ankylosing Spondylitis Patients

To study erectile function in male patients with Ankylosing Spondylitis (AS) trying to correlate it with sexual hormonal profile and disease activity. We included 35 AS patients and 104 controls. Patients and controls answered the IIEF (International Index of Erectile Dysfunction) and had dosing of total testosterone, free testosterone (FT), bioavailable testosterone (BT), SHBG (serum hormone binding globulin), albumin and LH (luteinizing hormone). AS patients had epidemiological, clinical and treatment data obtained from the charts. AS disease activity was measured simultaneously with blood collection through Bath AS Disease Activity Index, ASDAS (AS Disease Activity Score) -ESR (using erythrocyte sedimentation rate) and ASDAS-CRP (using C reactive protein). The IIEF results were worse in AS patients than controls (P = .02). Total testosterone and SHBG were higher in AS (with P = .01 and P <.0001 respectively). Between the 2 groups, no differences in LH, FT, BT levels (all with P = ns) were found. In AS patients, the IIEF results did not correlate with total testosterone, SHBG, LH, FT, and BT but a negative association was found with Bath AS Disease Activity Index (P = .001) and ASDAS-CRP (P = .02). AS patients had worst sexual performance than controls that was linked to disease activity but not to male sexual hormonal profile.

Effects of Thyroid Dysfunction on Reproductive Hormones in Female Rats.

Thyroid hormones (THs) play a critical role in the development of ovarian cells. Although the effects of THs on female reproduction are of great interest, the mechanism remains unclear. We investigated the effects of TH dysregulation on reproductive hormones in rats. Propylthiouracil (PTU) and L-thyroxine were administered to rats to induce hypo- and hyperthyroidism, respectively, and the reproductive hormone profiles were analyzed by radioimmunoassay (RIA). Ovarian histology was evaluated with hematoxylin and eosin (H&E) staining, and gene protein level or mRNA content was analyzed by western blotting or reverse transcription polymerase chain reaction (RT-PCR). The serum levels of gonadotropin releasing hormone (GnRH) and follicle stimulating hormone (FSH) in both rat models were significantly decreased on day 21, although there were no significant changes at earlier time points. There were no significant differences in luteinizing hormone (LH) or progesterone (P4) levels between the treatment and the control groups. Both PTU and L-thyroxine treatments downregulated estradiol (E2) concentrations; however, the serum testosterone (T) level was increased only in hypothyroid rats at day 21. In addition, the expression levels of FSH receptor, cholesterol side-chain cleavage enzyme (P450scc), and steroidogenic acute regulatory protein (StAR) were decreased in both rat models. Moreover, the onset of puberty was significantly delayed in the hypothyroid group. These results provide evidence that TH dysregulation alters reproductive hormone profiles, and that the initiation of the estrous cycle is postponed in hypothyroidism.

Study of hormone levels and semen parameters in infertile patients and fertile controls from Batna

Background: Male infertility or the inability of a man to procreate is a major public health problem and is a leading cause of marital discord in countries such as Algeria. Endocrine disorders that can be associated with significant medical pathology remain an important factor to be considered in the etiology of male infertility, and those disorders are usually associated with alteration of sperm count or in severe cases with azoospermia. In this study, we are evaluating semen parameters and hormonal levels of patients with idiopathic male infertility and comparing their results with healthy fertile controls.&#x0D; Methods: We aim to study the impact of hormones; follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and prolactin (PRL) on idiopathic male fertility and their impact on semen parameters, we conducted a study on 71 male subjects with 39 infertile men and 32 fertile controls from the city of Batna (Algeria). Our study lasted six months and was conducted at the University Hospital of Batna and a private analysis laboratory.&#x0D; Results: The results of semen analysis allowed us to determine that the most common pathology in our population is OANTS with a percentage of 21.05% followed by NS and NT with 13.16%; results of the permocytogramme show a predominance of atypical forms of the head with a frequency of 39.21%. Regarding the hormone dosage, prolactin was the most disturbed hormone with an average value of (18 ± 6.221 ng/ml), which is almost pathologic; the other hormones showed some disturbances but to a lesser degree. The results of spermiologique parameters of infertile men compared with fertile controls showed highly significant differences (P≤O.OOO1) regarding motility, concentration vitality, and spermatozoa morphology. The comparison of results of hormones between the two groups revealed differences in LH and prolactin levels; no differences were found regarding FSH and testosterones. Concerning the relationship between hormones and spermiologiques parameters, positive correlations were found between (LH and sperm concentration) (testosterone and sperm concentration), and, finally, a strong correlation was found between the levels of prolactin and the anomalies of intermediate piece of spermatozoa.&#x0D; Conclusion: This study showed that hormonal disorders are not a common cause of male infertility in our study population. It further showed the relative frequencies of the various semen abnormalities during the study period. Also, we found associations between altered semen parameters and pathological levels of some hormones; however, a complementary study with a more subjects is needed.

The Neonicotinoid Insecticide Imidacloprid: A Male Reproductive System Toxicity Inducer-Human and Experimental Study

Objective: This study was undertaken to explore relationships between level of imidacloprid in the serum and semen quality among men farmers in addition to investigating histopathological findings in treated mature male rats. Methods and results: Our research entailed two parts; firstly, human part done on farm workers (n=35) with age between (Mean ± SD 34.3±6.4) and healthy volunteers (n=25) their ages were (35.6±8.2) years old asked to provide semen and blood samples. A significant negative correlation between sperm concentration, motility, with serum and seminal Imidacloprid (IMI), its main metabolite 6-chloronicotinic acid (6- CINA) and cotinine , was identified in farmers (r= − 0.489; p<0.05). Second part of research was done on adult male rats that had been divided into a total of five groups 10 each. Two groups served as control one as negative and the other as positive. The other three experimental groups were given 45, 90 and 450 mg/kg body weight Imidacloprid in corn orally by a gavage process for fifteen days respectively. There was a significant difference in luteinizing hormone (LH), follicular stimulating hormone (FSH), testestrone (tes), Estradiol 2 (E2), prolactin and semen quality in IMI treated rats when compared to control groups. Vacuolar degeneration of germinal epithelium and loss of spermatids, seminiferous tubules suggesting inhibition of spermatogenesis was recorded in IMI treated rats. Conclusion: Toxic effects to male reproductive system can be considered as an outcome of IMI exposure and infertility problems can be expected in chronically exposed subjects.

Dolutegravir Has No Effect on the Pharmacokinetics of Oral Contraceptives With Norgestimate and Ethinyl Estradiol.

Background: Dolutegravir (DTG; Tivicay; ViiV Healthcare, Research Triangle Park, NC) is an HIV-1-unboosted integrase inhibitor with no cytochrome P450 or uridine 5′diphosphate-glucuronosyltransferase inhibition or induction. As DTG is administered to HIV-1–infected women receiving oral contraceptives, assessing the potential for drug interactions was warranted. Objective: To determine the impact of DTG on the pharmacokinetics (PK) and pharmacodynamics (PD) of a common oral contraceptive, norgestimate/ethinyl estradiol (NGM/EE; Ortho-Cyclen; Ortho-McNeil-Janssen Pharmaceuticals, Inc, Raritan, NJ). Methods: This randomized, 2-period, double-blind, placebo-controlled study was conducted within 1 menstrual cycle at 1 clinical center in the United States; 16 women were enrolled. Participants received NGM 0.25 mg/EE 0.035 mg throughout the study. During days 1 to 10, they were randomized to receive twice-daily DTG 50 mg or matching placebo with food and switched to the other treatment during days 12 to 21. Results: Ratios of area under the concentration-time curve from time 0 until end of the dosage interval (AUC0-τ), maximum plasma concentration, and concentration at the end of the dosage interval of norelgestromin with DTG treatment to the same PK parameters with placebo treatment were 0.975, 0.890, and 0.932, respectively; for EE, ratios were 1.03, 0.99, and 1.02, respectively. No significant differences in luteinizing hormone, follicle-stimulating hormone, and progesterone were detected on days 1, 10, 11, 21, and 22. DTG steady-state AUC0-τ was similar to historical data. No severe or grade 3/4 adverse events occurred. Conclusions: DTG had no effect on NGM/EE PK or PD. NGM/EE can be administered with DTG without dose adjustment.

Luteal phase dynamics of follicle‐stimulating and luteinizing hormones in obese and normal weight women

Female obesity is a state of relative hypogonadotrophic hypogonadism. The aim of this study is to examine gonadotrophin secretion and response to gonadotrophin-releasing hormone (GnRH) in the luteal phase of the menstrual cycle and to investigate the pharmacodynamics and pharmacokinetics of endogenous and exogenous luteinizing hormone (LH) in obese women. Participants underwent a luteal phase frequent blood sampling study. Endogenous LH pulsatility was observed, gonadotrophin-releasing hormone (GnRH) was given in two weight-based doses, and GnRH antagonist was administered followed by recombinant LH. Regularly menstruating obese (n = 10) and normal weight (n = 10) women. Endogenous hypothalamic-pituitary function (as measured by LH pulsatility), pituitary sensitivity (GnRH-induced LH secretion), pharmacodynamics of endogenous LH and pharmacokinetics of exogenous LH were compared between the obese and normal weight groups. There were no statistically significant differences in endogenous LH pulsatility or pituitary responses to two weight-based doses of GnRH between the obese and normal weight women. There were no differences in the pharmacodynamics of endogenous LH or the pharmacokinetics of exogenous LH between the groups. FSH dynamics did not differ between the groups throughout the study. The relative hypogonadotrophic hypogonadism of obesity cannot be explained by differences in LH and FSH luteal phase dynamics or differences in endogenous LH pharmacodynamics or exogenous LH pharmacokinetics.

Comparison of serum free testosterone, luteinizing hormone and follicle stimulating hormone levels in diabetics and non-diabetics men- a case-control study.

Diabetic men have been claimed to have lower serum free testosterone (FT) concentrations than non-diabetic men. The aim of this study was to investigate if serum FT, luteinizing hormone (LH), and follicle stimulating hormone (FSH) concentrations are different in patients with type 2 diabetes mellitus compared with healthy men and to identify factors associated with low serum testosterone concentrations in men with type 2 diabetes. Serum FT, LH and FSH concentrations in 65 men with type 2 diabetes between 50 and 55 years compared with 65 non-diabetic men in Valye-Asr Hospital in Birjand, Iran during October 2009 to August 2010. In addition, the relationships between serum FT concentrations with LH and FSH concentrations as well as other factors including age, fast blood sugar and glycemic control (HbA1C) were investigated. Serum FT concentrations were significantly lower in type 2 diabetic patients (2.53±1.68 pg/ml) than in healthy men (4.29±2.43 pg/ml) (P<0.001). There were not any significant differences in LH and FSH concentrations between the two groups. There was a significant negative relationship between serum FT and HbA1C, but this relation for LH and FSH was positive and non-significant (P<0.001). Serum FT concentration is lower in type 2 diabetic patients compared with non-diabetic men suggesting further research to better understand the underlying biologic mechanisms.

Night Shift Work and Hormone Levels in Women

Night shift work may disrupt the normal nocturnal rise in melatonin, resulting in increased breast cancer risk, possibly through increased reproductive hormone levels. We investigated whether night shift work is associated with decreased levels of urinary 6-sulfatoxymelatonin, the primary metabolite of melatonin, and increased urinary reproductive hormone levels. Participants were 172 night shift and 151 day shift-working nurses, aged 20-49 years, with regular menstrual cycles. Urine samples were collected throughout work and sleep periods and assayed for 6-sulfatoxymelatonin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrone conjugate (E1C). 6-Sulfatoxymelatonin levels were 62% lower and FSH and LH were 62% and 58% higher, respectively, in night shift-working women during daytime sleep than in day shift-working women during nighttime sleep (P ≤ 0.0001). Nighttime sleep on off-nights was associated with 42% lower 6-sulfatoxymelatonin levels among the night shift workers, relative to the day shift workers (P < 0.0001); no significant differences in LH or FSH were observed. 6-Sulfatoxymelatonin levels during night work were approximately 69% lower and FSH and LH were 35% and 38% higher, compared with day shift workers during nighttime sleep. No differences in E1C levels between night and day shift workers were observed. Within night shift workers, 6-sulfatoxymelatonin levels were lower and reproductive hormone levels were higher during daytime sleep and nighttime work, relative to nighttime sleep (P < 0.05). These results indicate that night shift workers have substantially reduced 6-sulfatoxymelatonin levels during night work and daytime sleep and that levels remain low even when a night shift worker sleeps at night. Shift work could be an important risk factor for many other cancers in addition to breast cancer.

Sexual differentiation of the gonadotropin surge release mechanism: A new role for the canonical NfκB signaling pathway

Sex differences in luteinizing hormone (LH) release patterns are controlled by the hypothalamus, established during the perinatal period and required for fertility. Female mammals exhibit a cyclic surge pattern of LH release, while males show a tonic release pattern. In rodents, the LH surge pattern is dictated by the anteroventral periventricular nucleus (AVPV), an estrogen receptor-rich structure that is larger and more cell-dense in females. Sex differences result from mitochondrial cell death triggered in perinatal males by estradiol derived from aromatization of testosterone. Herein we provide an historical perspective and an update describing evidence that molecules important for cell survival and cell death in the immune system also control these processes in the developing AVPV. We conclude with a new model proposing that development of the female AVPV requires constitutive activation of the Tnfα, Tnf receptor 2, NfκB and Bcl2 pathway that is blocked by induction of Tnf receptor-associated factor 2-inhibiting protein (Traip) in the male.

The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

IntroductionThis study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy. Patients and methodsA retrospective evaluation of reproductive hormones in patients with unilateral stage I TGCC (N=72) without relapse diagnosed between 1990 and 2008. A group of healthy males (N=706) served as controls. ResultsBefore orchiectomy there were no significant differences in luteinizing hormone (LH) and testosterone (T) levels between human chorionic gonadotropin (hCG)-negative patients and controls, although 33% of the patients were outside the 97.5 percentile when using bivariate LH/T evaluation. At 1-year follow-up there was a significant increase in LH (ΔLH=2.04IU/L, p<0.001), and 57% of the patients had an LH/T relation outside the 97.5 percentile. ConclusionPatients with stage I TGCC are at increased risk of having an LH/T relation outside the normal range one year after orchiectomy, suggesting insufficient Leydig-cell function. Whether a proportion of these patients will develop manifest hypogonadism and benefit from androgen therapy is yet to be clarified.

Absence of Apparent Circadian Rhythms of Gonadotropins and Free α-Subunit in Postmenopausal Women: Evidence for Distinct Regulation Relative to Other Hormonal Rhythms

Aging is associated with a decrease in gonadotropin levels in postmenopausal women (PMW) and is also associated with alterations in a number of circadian rhythms. The goals of this study were to determine the presence of circadian rhythms of gonadotropins and glycoprotein free alpha-subunit (FAS) in young and old PMW. Healthy, euthyroid PMW, ages 45 to 55 years (n = 11) and 70 to 80 years (n = 11), were admitted in the morning to start a 24-h constant routine of light, temperature, position, and activity. Subjects remained awake and semirecumbent for the duration of the study and were fed hourly snacks, and activity was monitored continuously. Blood was sampled every 5 min for two 8-h periods corresponding to the estimated acrophase and nadir of the temperature rhythm. Luteinizing hormone (LH) and FAS were measured in all samples and follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and cortisol in 20-min serum pools. Mean LH (p < 0.001), FSH (p < 0.002), and FAS (p < 0.002) were lower in older compared with younger PMW. Day/night differences in cortisol and TSH (p < 0.001) were present in all subjects. However, there were no day/night differences in LH in younger or older PMW or in FSH in younger or older PMW. There were no day/night differences in mean FAS in younger or older PMW or in FAS pulse frequency or amplitude. Thus, in controlled studies in which differences in cortisol and TSH were demonstrated, there were no day/night differences in LH, FSH, or FAS in PMW. These studies suggest that despite evidence of intact circadian rhythms of cortisol and TSH, gonadotropin secretion does not appear to follow a circadian pattern in PMW. Thus, the age-related decline in gonadotropin secretion in PMW is not associated with a dampening of circadian rhythmicity. The absence of day/night differences in FAS suggests that GnRH plays a more prominent role in FAS regulation than does thyrotropin-releasing hormone in PMW.

Neuroendocrine responses to psychological stress in eumenorrheic and oligomenorrheic women

Neuroendocrine adaptive responses to psychological stress include activation of the hypothalamic–pituitary–adrenal (HPA) axis and sometimes suppression of the hypothalamic–pituitary–gonadal (HPG) axis. In women who experience chronic stress, these responses are probably responsible for disturbances in the menstrual cycle. In the present experiment, we investigated the effect of an acutely stressful situation on the physiological and neuroendocrine responses in college age women. We hypothesized that females who are experiencing some degree of abnormal menstrual function or women who have less-robust cycles (oligomenorrheic females) would exhibit differences in gonadotropin secretion from eumenorrheic females when exposed to psychological stressors. Fifteen women completed this study: eumenorrheic (n = 5) and oligomenorrheic women (n = 5) who experienced a series of psychological stressors, and eumenorrheic controls (n = 5). Blood samples were taken at 10 min intervals for 8 h (09:00–17:00) in each woman during the mid-follicular phase of the menstrual cycle. The psychological stressors were administered for 1 h beginning at 13:00 h. Luteinizing hormone (LH), growth hormone (GH) and cortisol were measured in each sample to assess the effect of stress on secretion of these hormones. Deconvolution analysis was used to analyze pulsatile hormone secretion and the approximate entropy (ApEn) statistic analyzed the regularity of release of each hormone. Although, there were significant changes in heart rate (HR), skin resistance (SR) and cortisol levels in the stressed women during the psychological stressor compared to resting baseline values but not in the controls, there was no difference in either LH or GH secretion between women who experienced stress and those who did not. Furthermore, there were no differences in the LH or GH secretion patterns in the oligomenorrheic and eumenorrheic women exposed to the psychological stressor.

Polycystic Ovarian Morphology With Regular Ovulatory Cycles

This study was an attempt to determine whether polycystic ovarian morphology (PCOM) is an important factor in the development of polycystic ovarian syndrome (PCOS). Among the 68 women studied, all of whom had regular ovulatory menstrual cycles and lacked clinical signs of hyperandrogenism, 39 had PCOM and 29 had morphologically normal ovaries. Ovarian morphology was examined by ultrasonography, usually performed transvaginally. Hormone levels were estimated at baseline in the early follicular phase (EFP) of the cycle and, in 36 women, studies were repeated each day during a complete cycle. Body mass index did not differ in women with PCOM and those with normal ovaries. Ovarian volume was twice as great in the PCOM group, and these women had higher numbers of follicles than did those with normal ovaries (8-15 vs. 4-8 per ovary). Baseline EFP levels of testosterone, free testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS) were higher in women with PCOM, and levels of sex hormone-binding globulin (SHBG) were lower. Four PCOM women had elevated testosterone levels. The difference in DHEAS levels was independent of age. Sampling across the cycle disclosed no significant group differences in luteinizing hormone, follicle-stimulating hormone, progesterone, or estradiol. In EFP and also at midcycle, women with PCOM had significantly higher testosterone levels compared with those with normal ovaries. SHBG levels tended to be lower in women with PCOM across the cycle, but not significantly so. Levels of free testosterone were higher in women with PCOM, especially in the EFP. Fasting insulin and insulin resistance were higher in women with PCOM; both parameters correlated inversely with SHBG. No group differences were found in blood pressure or serum lipid levels. Women with PCOM had greater androstenedione, testosterone, and 17-hydroxyprogesterone responses to human chorionic gonadotropin compared with women with normal ovaries. These findings indicate that PCOM is the mildest form of ovarian hyperandrogenism. Whether PCOM favors the development of PCOS remains to be determined.